归脾汤通过调控AMPK/mTOR通路改善产后子宫复旧不全的机制研究OA
A Study on the Mechanism of Gui-Pi Decoction in Improving Incomplete Uterine Involution Postpartum by Regulating the AMPK/mTOR Pathway
目的:观察归脾汤对大鼠产后子宫复旧不全的治疗作用及机制.方法:建立产后子宫复旧不全模型,随机分为模型组、归脾汤低(4.6g/kg)、高剂量(9.3g/kg)组和归脾汤高剂量(9.3g/kg)+AMPK 抑制剂(Compound C,10mg/kg)组,另取正常大鼠作为对照组,每组 10 只.各组灌胃/腹腔注射相应药物或生理盐水,早晚各 1 次,连续 7d.观察并计算子宫出血量;ELISA 法检测血清 TNF-α、IL-1β、IL-6 水平;HE 染色观察子宫组织病理形态;TUNEL 染色检测子宫组织凋亡水平;免疫组化法检测子宫组织 Bax、Bcl-2、裂解的半胱天冬酶-3(Cleaved caspase-3)蛋白表达;Western blot 法检测子宫组织腺苷酸活化蛋白激酶(AMPK)、哺乳动物雷帕霉素靶蛋白(mTOR)及其磷酸化蛋白表达.结果:与对照组比较,模型组大鼠出血量及血清 TNF-α、IL-1β、IL-6 水平均升高(P<0.05);子宫组织内膜增厚,腺体扭曲,肌层紊乱,大量炎细胞浸润,且细胞凋亡率、Bax、Cleaved caspase-3、p-mTOR/mTOR 蛋白比值均升高(P<0.05),Bcl-2、p-AMPK/AMPK 蛋白比值均降低(P<0.05).与模型组比较,归脾汤低、高剂量组大鼠出血量及血清 TNF-α、IL-1β、IL-6 水平均降低(P<0.05);子宫组织内膜变薄,腺体恢复,肌层整齐,炎细胞减少,且细胞凋亡率、Bax、Cleaved caspase-3、p-mTOR/mTOR 蛋白比值均降低(P<0.05),Bcl-2、p-AMPK/AMPK 蛋白比值均升高(P<0.05).归脾汤对子宫复旧不全大鼠的改善作用呈剂量依赖性(P<0.05),且 Compound C 可逆转归脾汤的作用效果(P<0.05).结论:归脾汤可促进大鼠产后子宫复旧,抑制炎症反应及凋亡,其作用机制可能与调控 AMPK/mTOR 通路相关.
Objective:To investigate the therapeutic effect and underlying mechanism of Gui-Pi Decoc-tion(GPD)on postpartum uterine involution deficiency in rats.Methods:A rat model of postpartum uterine involution deficiency was established and randomly divided into model group,GPD-low-dose(4.6g/kg)group,GPD-high-dose(9.3g/kg)group,and GPD-high-dose(9.3g/kg)plus AMPK inhibitor(Com-pound C,10mg/kg)group;normal rats served as the control group(n=10 each).All groups received corre-sponding drugs or saline by gavage/intraperitoneal injection twice daily for 7 consecutive days.Uterine bleed-ing volume was recorded.Serum TNF-α,IL-1β,and IL-6 levels were measured by ELISA.Uterine histopa-thology was evaluated by HE staining;apoptosis was detected by TUNEL.Immunohistochemistry was used to examine uterine expression of Bax,Bcl-2,and cleaved caspase-3.Western blot was used to determine uter-ine AMPK,mTOR,and their phosphorylated proteins.Results:Compared with the control group,the model group exhibited increased bleeding volume and elevated serum TNF-α,IL-1β and IL-6(P<0.05);thick-ened endometrium,distorted glands,disordered myometrium,massive inflammatory infiltration,higher apop-totic rate,up-regulated Bax and cleaved caspase-3,increased p-mTOR/mTOR ratio(P<0.05),and down-regulated Bcl-2 and p-AMPK/AMPK ratio(P<0.05).Compared with the model group,both GPD doses reduced bleeding volume and serum TNF-α,IL-1β and IL-6 levels(P<0.05),attenuated endometrium,and contributed to the well-defined muscle layer and reduced inflammatory cells,diminished apoptosis and Bax/cleaved caspase-3 expression,decreased p-mTOR/mTOR ratio(P<0.05),and elevated Bcl-2 and p-AMPK/AMPK ratio(P<0.05)in a dose-dependent manner;these beneficial effects can be reversed by Compound C(P<0.05).Conclusion:Gui-Pi Decoction promotes postpartum uterine involution in rats by suppressing inflammation and apoptosis,an effect likely mediated through modulation of the AMPK/mTOR pathway.
刘丽洁;刘晶;褚伟莎;马淑英;谷向向
河北省石家庄市妇幼保健院产科,河北 石家庄 050000河北省霸州市第三医院妇产科,河北 霸州 510080河北省石家庄市妇幼保健院产科,河北 石家庄 050000河北省盐山县人民医院,河北 盐山 061300河北省石家庄市妇幼保健院产科,河北 石家庄 050000
产后子宫复旧不全归脾汤炎症因子凋 亡AMPK/mTOR 通路
Postpartum uterine involution deficiencyGui-Pi decoctionInflammatory cyto-kinesApoptosisAMPK/mTOR pathway
《河北医学》 2026 (5)
738-744,7
2024年度中医药类科学研究课题(编号:2024134)
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